The goal of this study is a better understanding of the mechanisms underlying ageing of the brain. The studies focus on Alzheimer's dementia and on the Batten - Speilmeyer - Vogt - Kufs syndrome. The investigations are clinical, biochemical, light microscopic, ultrastructural and experimental in scope and employ animal models as well. One of many ageing theories is that free-radicals are damaging to subcellular enzymes, membranes and DNA. The result is liberation of proteins, lipids and nucleotides which ultimately become autoxidized, cross-linked, and phagocytized into lipopigment granules. Hydrogen peroxide can generate free-radicals. If enzymes regulating intracellular peroxide levels decrease with age, then peroxides, and free-radicals would accumulate linearly, and produce "age" pigment. Natural lipid soluble antioxidants (Vitamin E) do not increase with age, so that ageing may be caused by increasing levels of toxic compounds together with relative decreasing levels of regulatory enzymes and antioxidants. Studies of the role of tubulin at the nerve ending in relation to the formation of twisted tubules will continue. Primary emphasis will be on the modification reactions that tubulin undergoes prior to incorporation into the synaptic plasma membrane and the effects of these modifications on the polymerization properties of tubulin in vitro.